Gils Ann, Vande Casteele Niels, Poppe Raf, Van de Wouwer Marlies, Compernolle Griet, Peeters Miet, Brouwers Els, Vermeire Séverine, Geukens Nick, Declerck Paul J
*Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven; †PharmAbs, The KU Leuven Antibody Center, University of Leuven; and ‡Department of Gastroenterology, University Hospitals Leuven, Belgium.
Ther Drug Monit. 2014 Oct;36(5):669-73. doi: 10.1097/FTD.0000000000000074.
Therapeutic drug monitoring of adalimumab (ADM) has been introduced recently. When no detectable ADM serum concentrations can be found, the formation of antidrug antibodies (ADA) should be investigated. A variety of assays to measure the occurrence of ADA have been developed. Results are expressed as arbitrary units or as a titration value. The aim was to develop a monoclonal antibody (MA) that could serve as a universal calibrator to quantify the amount of ADA in ADM-treated patients.
Hybridoma technology was used to generate a MA toward ADM. The functionality of the MA was tested in a bridging enzyme linked immunosorbent assay (ELISA) setup and in a cell-based assay. Sera from 25 anti-tumor necrosis factor naive patients with inflammatory bowel disease were used to determine the cutoff values. Sera from 9 ADM-treated patients with inflammatory bowel disease, with undetectable serum concentrations of ADM were used to quantify the ADA response.
In this study, MA-ADM6A10, an IgG1 that can be used as a calibrator in both an ELISA to quantify the amount of binding antibodies and in a cell-based assay to quantify the amount of neutralizing antibodies, was generated. Combining the results of both assays showed that the sera with high concentrations of anti-ADM binding antibodies also had the highest neutralizing capacity.
The availability of a universal calibrator could facilitate the interlaboratory harmonization of antibody titers in patients who develop anti-adalimumab antibodies.
阿达木单抗（ADM）的治疗药物监测最近已被引入。当无法检测到ADM血清浓度时，应调查抗药物抗体（ADA）的形成情况。已经开发了多种检测ADA发生情况的检测方法。结果以任意单位或滴定值表示。目的是开发一种单克隆抗体（MA），可作为通用校准物来量化接受ADM治疗患者体内ADA的量。
采用杂交瘤技术制备针对ADM的单克隆抗体。在桥接酶联免疫吸附测定（ELISA）设置和基于细胞的测定中测试该单克隆抗体的功能。使用25例未接受过抗肿瘤坏死因子治疗的炎症性肠病患者的血清来确定临界值。使用9例接受ADM治疗且血清中ADM浓度无法检测到的炎症性肠病患者的血清来量化ADA反应。
在本研究中，产生了MA-ADM6A10，这是一种IgG1，可在ELISA中用作校准物以量化结合抗体的量，并在基于细胞的测定中用作校准物以量化中和抗体的量。结合两种检测结果表明，抗ADM结合抗体浓度高的血清也具有最高的中和能力。
通用校准物的可用性可促进在产生抗阿达木单抗抗体的患者中抗体滴度的实验室间标准化。
